Lymphoma can involve any part of the musculoskeletal system. Primary musculoskeletal lymphoma is rare but can occur in bone (reticulum cell sarcoma) or in the skin and subcutaneous tissues (mycosis fungoides). Secondary involvement in the musculoskeletal system is more common and can have a variety of radiologic findings. The definitive diagnosis of musculoskeletal lymphoma, however, is difficult to make by using imaging criteria alone. Any part of the musculoskeletal system can be involved and, therefore, a wide variety of primary and secondary neoplasms or inflammatory processes may have similar radiologic findings. The main differential diagnostic considerations, depending on the age of the patient and the clinical presentation, include osteosarcoma, Ewing's tumor, metastatic disease (from breast, lung, thyroid, or renal primary lesions), as well as chronic osteomyelitis or myositis. Primary and secondary bone lymphoma can be indistinguishable radiologically and histologically, but modern imaging techniques allow more accurate differentiation of primary from secondary bone involvement. This pictorial essay illustrates the CT findings of primary and secondary lymphoma involving bone, muscle, and skin and subcutaneous tissues.